Illustrative examples of diffusional drug delivery devices are found in U.S. Pat. Nos. 3,598,122, 3,598,123, 3,742,951, 3,948,262, 4,031,8942 4,144,317, 4,201,211, 4,286,592, 4,314,557, 4,379,454, and 4,568,343, for example, which are incorporated herein by reference. In these devices, a drug or other active agent is released by diffusion from a reservoir through the agent-releasing surface of the device to the biological environment at which the device is applied. Such devices perform well in the administration of many agents but are not suitable for the administration of an agent whose dosage regime requires that the onset of therapeutic effect be delayed for a significant period of time after application of the device at the site of delivery. This is because the surface through which the agent is released, at the time of application, contains the agent in an amount that is significant compared to the amount in the body that gives rise to a therapeutic concentration. In those devices which utilize an agent reservoir which contains an agent at a concentration above the saturation concentration of the agent in the material from which the reservoir is formed, the agent will be present at the agent-releasing surface at the saturation concentration of the agent in the material from which the releasing surface is formed. Saturation concentration is equivalent to a thermodynamic activity of 1 (unit activity). When prior art diffusional devices are applied, agent is immediately available for diffusion into the body and the concentration of the agent at the releasing surface rapidly decreases as the concentration gradient required for steady-state diffusional delivery is established by the absorption of the agent from the releasing surface into the body. In some cases the initial rate of release is unacceptably high, and a method for reducing this initial "burst" of agent delivery is described in U.S. Pat. No. 3,923,939 to Baker et al. Even in the Baker patent, the agent-releasing surface of the diffusional embodiment contains the agent at the saturation concentration of the agent in the material in which it is dispersed, and delivery commences immediately in the manner described above.
Non-diffusional devices are known which do not immediately present drug to the biological environment when installed, such as devices which contain material in breakable microcapsules or have a fluid-imbibing pump described in commonly assigned U.S. Pat. No. 4,655,766. Diffusional delivery devices known to the prior art, however, do not possess this capability.
One of the advantages of a continuous release dosage form, such as a transdermal drug delivery device, is the improvement in patient compliance that is obtained from the concurrent removal of one device and application of a new device at the same time. This advantage is lost when removal and application occur at different times or where onset of a therapeutic effect is desired at an inconvenient time such as shortly prior to awakening. It is not possible, using concurrent application and removal of diffusional delivery devices of the prior art to substantially delay the onset of transdermal drug delivery from the time of application, such as at bedtime, until a later, often inconvenient, time, such as shortly prior to awakening. While other, non-diffusional delivery devices exist which can deliver drug after an extended delay, diffusional devices of the prior art do not possess this capability and rapidly commence delivering the drug at their intended therapeutic rates.
There is, therefore, a continuing need to provide a diffusional agent delivery device which provides for delayed onset of active agent administration and release of active agent at the desired rate at a predetermined interval after application.